Acute onset demyelinating encephalomyelitis with morphologic features similar to multiple sclerosis was first observed in group-housed Japanese macaques in 1986. The incidence of the disease peaked the following year, affecting 3% of the population. Subsequently, approximately 1% of the population developed demyelinating encephalomyelitis annually. The age of the affected animals ranged from 97 days to 20 years, with equal sex distribution. Using long-term explant culture techniques, a highly cell-associated spumaretrovirus was recovered from explant cultures of lesioned brain and spinal cord tissues in six of eight animals. No viruses were isolated from CNS explant cultures of nonlesioned tissue from affected animals or from normal controls. To prospectively evaluate the relationship between spumaretrovirus infection and encephalomyelitis, virus isolations from peripheral blood leukocytes were conducted on 203 animals in the troop in 1994; spumaretrovirus was isolated from 32 (15.8%). Of the 32 infected animals, 24 (75%) were less than 7 years of age. Virus isolations were repeated on 228 animals in 1995. Spumaretrovirus was isolated from 43 (18.9%) and a novel herpesvirus was recovered from 10 (4.4%). Two animals developed demyelinating encephalomyelitis in 1995. Both were herpesvirus-infected animals and Herpesvirus was isolated from lesioned brain and spinal cord, suggesting additional agents must be considered in the etiology of this disease.